Fig. 1

a Schematic representation of SHP2 activation. In the Apo-state, SHP2 remains in a closed autoinhibited conformation. Peptide binding can either stabilize this autoinhibited state or induce a conformational transition of the N-SH2 domain to the α-state, weakening N-SH2–PTP interactions. This transition exposes the catalytic site, leading to SHP2 activation. b Location of PTPN11 pathogenic variants mapped to exons and SHP-2 functional domains. The top bar represents PTPN11 exons, with the coding region in pink. Blue boxes indicate the number of patients with each pathogenic variant. Below, the SHP-2 protein structure is shown, highlighting the N-SH2, C-SH2, and PTP domains [19, 20]